Low prevalence of necrolytic acral erythema in patients with chronic hepatitis C virus infection

Abstract

Background Chronic hepatitis C virus (HCV) infection is associated with necrolytic acral erythema (NAE). However, the prevalence of NAE among HCV patients is unknown, and the clinical and histological features have not been well defined. Objective To determine the prevalence, overall clinical features, and cutaneous histopathological characteristics of NAE patients. Methods A cross-sectional study was performed among chronic HCV-infected patients cared for at three Philadelphia hospitals. Patients completed a questionnaire and underwent a dermatologic examination. All undiagnosed skin lesions with clinical features of NAE as described in the literature underwent skin biopsy. Results Among 300 patients with chronic HCV infection (median age, 55 years; 73% male; 70% HCV genotype 1), five (prevalence, 1.7%; 95% CI, 0.5 – 3.8%) had skin lesions consistent with NAE clinically, which were analyzed and confirmed with skin biopsy. All five skin biopsies demonstrated variable psoriasiform hyperplasia, mild papillomatosis, parakeratosis, and necrotic keratinocytes in the superficial epidermis. All 5 patients were >40 years old, African American males, infected with HCV genotype 1 and had a high viral load (>200,000 IU/mL). Limitations Previous descriptions of NAE were used to guide the evaluation and need for a biopsy; however, other unknown clinical characteristics of the disease may exist. The senior author was the sole interpreter of the biopsies. Only 300 of the 2500 eligible patients enrolled in the study. Conclusion The prevalence of NAE among chronic HCV patients in this sample was very low. Further research is needed to determine the etiology and appropriate therapies of NAE.

Necrolytic acral erythema: a rare skin disease associated with hepatitis C virus infection

“…5 A study recently published showed a prevalence of 1.7% for necrolytic acral erythema among patients with infections caused by hepatitis C virus. 1 The most common location of lesions is the back of feet and toes, but they can also affect the surface of the Achilles tendon, the malleolus, legs and knees. Associated symptoms are pruritus, pain, burning and dysesthesia.…”

“…1 It is characterized, in the initial phases, by erythematous or violaceous papules, bullae and erosions. In the late phase, there is onset of well-delimited plaques with erythema on their outer rim, lichenification, secondary hyperpigmentation and fine desquamation on the surface.…”

Hepatitis C virus and its cutaneous manifestations: treatment in the direct‐acting antiviral era

“…There is currently no standard treatment for NAE, although oral zinc, antivirals, topical steroids and phototherapy have been proposed without compelling evidence. The existing literature has contradicting reports as to the efficacy of oral zinc, and phototherapy and topical steroids have shown minimal efficacy . Use of interferon has also been equivocal, with the suggestion that SVR may correlate with clinical improvement, while other reports find interferon regimens ineffective …”

“…4,25,28,29 The pathophysiology is unclear, with both direct and indirect theories proposed. The direct theory, supported by evidence that HCV is lymphotropic and that the cryoprecipitate Lichen Planus 2.5-to 4.5-fold increased risk 55,56 Fivefold increased risk 55,56 Porphyria Cutanea Tarda <1-5% 62 50% HCV RNA positivity Up to 275-fold increased risk 62 Necrolytic Acral Erythema 0.2-1.7% 4,91 Near 100% (initially considered pathognomonic for HCV) 86,89,91 Cutaneous HCV in the New Antiviral Era contains high concentrations of viral genome, posits that HCV induces B cells to produce immunoglobulins. Alternatively, the indirect theory proposes that the virus provokes MC via chronic immune stimulation.…”

“…The existing literature has contradicting reports as to the efficacy of oral zinc, and phototherapy and topical steroids have shown minimal efficacy. 86,88,89,91 Use of interferon has also been equivocal, 86,88,92 with the suggestion that SVR may correlate with clinical improvement, 92 while other reports find interferon regimens ineffective. 93 There is limited literature on the use of new DAAs in HCV-NAE patients, although one report demonstrated resolution of NAE with ledipasvir, sofosbuvir and ribavirin.…”